Skip to main content
Log in

The role of cardiac autonomic function in hypertension and cardiovascular disease

Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Autonomic nervous system abnormality, clinically manifested as a hyperkinetic circulation characterized by elevations in heart rate, blood pressure, plasma norepinephrine levels, and cardiac output, has been repeatedly demonstrated in hypertension. Increased release of norepinephrine from the brain has also been described in hypertension, and increased sympathetic activity has been demonstrated using spectral analysis of heart rate variability, particularly in the early stage of hypertension and in white-coat hypertension. Studies performed with microneurographic assessment also have found a marked increase in muscle sympathetic nervous activity in subjects with both borderline and established hypertension. A transition from the early hyperkinetic state to a high-resistance, established hypertension has been documented in longitudinal studies. The high blood pressure induces vascular hypertrophy, which in turn leads to increased vascular resistance. Cardiac output returns from elevated to normal values as β-adrenergic receptors are downregulated and stroke volume decreases. In parallel with the hemodynamic transition, the sympathetic tone is reset in the course of hypertension. Autonomic nervous system abnormality is also associated with such pressure-unrelated cardiovascular risk factors as tachycardia, high hematocrit, insulin resistance, and obesity. Mechanisms of this association are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References and Recommended Reading

  1. Julius S, Conway J: Hemodynamic studies in patients with borderline blood pressure elevation. Circulation 1968, 38:282–288.

    PubMed  CAS  Google Scholar 

  2. Julius S, Pascual AV, London R: Role of parasympathetic inhibition in the hyperkinetic type of borderline hypertension. Circulation 1971, 44:413–418.

    PubMed  CAS  Google Scholar 

  3. Goldstein DS: Plasma catecholamines and essential hypertension: an analytical review. Hypertension 1983, 5:86–99.

    PubMed  CAS  Google Scholar 

  4. Julius S, Krause L, Schork N, et al.: Hyperkinetic borderline hypertension in Tecumseh, Michigan. J Hypertens 1991, 9:77–84.

    PubMed  CAS  Google Scholar 

  5. Palatini P, Vriz O, Nesbitt S, et al.: Parental hyperdynamic circulation predicts insulin resistance in offspring: the Tecumseh Offspring Study. Hypertension 1999, 33:769–774.

    PubMed  CAS  Google Scholar 

  6. Grassi G: Role of the sympathetic nervous system in human hypertension. J Hypertens 1998, 16:1979–1987.

    Article  PubMed  CAS  Google Scholar 

  7. Schork NJ, Weder AB, Schork MA, et al.: Disease entities, mixed multi-normal distributions, and the role of the hyperkinetic state in the pathogenesis of hypertension. Stat Med 1990, 9:301–314.

    Article  PubMed  CAS  Google Scholar 

  8. Masuo K, Kawaguchi H, Mikami H, et al.: Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003, 42:474–480.

    Article  PubMed  CAS  Google Scholar 

  9. Julius S, Nesbitt S: Sympathetic overactivity in hypertension. A moving target. Am J Hypertens 1996, 9:113s–120s.

    Article  PubMed  CAS  Google Scholar 

  10. Jennings GL: Noradrenaline spillover and microneurography measurements in patients with primary hypertension. J Hypertens 1998, 16(Suppl):S35–S38.

    Google Scholar 

  11. Kjeldsen SE, Zweifler AJ, Petrin J, et al.: Sympathetic nervous system involvement in essential hypertension: increased platelet noradrenaline coincides with decreased beta-adrenoreceptor responsiveness. Blood Press 1994, 3:164–171.

    Article  PubMed  CAS  Google Scholar 

  12. Esler M: The sympathetic system and hypertension. Am J Hypertens 2000, 13:99S–105S.

    Article  PubMed  CAS  Google Scholar 

  13. Palatini P, Majahalme S, Amerena J, et al.: Determinants of left ventricular structure and mass in young subjects with sympathetic over-activity. The Tecumseh Offspring Study. J Hypertens 2000, 18:769–775.

    Article  PubMed  CAS  Google Scholar 

  14. Palatini P, Longo D, Zaetta V, et al.: Evolution of blood pressure and cholesterol in stage 1 hypertension: role of autonomic nervous system activity. J Hypertens 2006, 24:1375–1381.

    PubMed  CAS  Google Scholar 

  15. Maver J, Strucl M, Accetto R: Autonomic nervous system activity in normotensive subjects with a family history of hypertension. Clin Auton Res 2004, 14:369–375.

    Article  PubMed  Google Scholar 

  16. Mancia G, Grassi G, Giannattasio C, Seravalle G: Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 1999, 34:724–728.

    PubMed  CAS  Google Scholar 

  17. Neumann SA, Jennings JR, Muldoon MF, Manuck SB: White-coat hypertension and autonomic nervous system dysregulation. Am J Hypertens 2005, 18:584–588.

    Article  PubMed  Google Scholar 

  18. Fagard RH, Stolarz K, Kuznetsova T, et al.: Sympathetic activity, assessed by power spectral analysis of HR variability, in white-coat, masked, and sustained hypertension versus true normotension. J Hypertens 2007, 25:2280–2285.

    Article  PubMed  CAS  Google Scholar 

  19. Calhoun DA, Mutinga ML, Wyss JM, Oparil S: Muscle sympathetic nervous system activity in black and Caucasian hypertensive subjects. J Hypertens 1994, 12:1291–1296.

    Article  PubMed  CAS  Google Scholar 

  20. Flaa A, Mundal HH, Eide I, et al.: Sympathetic activity and cardiovascular risk factors in young men in the low, normal, and high blood pressure ranges. Hypertension 2006, 47:396–402.

    Article  PubMed  CAS  Google Scholar 

  21. Lund-Johansen P: Newer thinking on the hemodynamics of hypertension. Curr Opin Cardiol 1994, 9:505–511.

    Article  PubMed  CAS  Google Scholar 

  22. Julius S: The blood pressure seeking properties of the central nervous system. J Hypertension 1988, 6:177–185.

    Article  CAS  Google Scholar 

  23. Palatini P, Julius S: Heart rate and the cardiovascular risk. J Hypertens 1997, 15:3–17.

    Article  PubMed  CAS  Google Scholar 

  24. Palatini P, Benetos A, Grassi G, et al.: Identification and management of the hypertensive patient with elevated heart rate: statement of a European Society of Hypertension Consensus Meeting. J Hypertens 2006, 24:603–610.

    Article  PubMed  CAS  Google Scholar 

  25. Levy RL, White PD, Stroud WD, Hillman CC: Transient tachycardia: prognostic significance alone and in association with transient hypertension. JAMA 1945, 129:585–588.

    Google Scholar 

  26. Dyer AR, Persky V, Stamler J, et al.: Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiological studies. Am J Epidemiol 1980, 112:736–749.

    PubMed  CAS  Google Scholar 

  27. Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA: Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987, 113:1489–1494.

    Article  PubMed  CAS  Google Scholar 

  28. Mancia G, Bertinieri G, Grassi G, et al.: Effects of blood pressure measurement by the doctor on patient’s blood pressure and heart rate. Lancet 1983, 2(8352):695–697.

    Article  PubMed  CAS  Google Scholar 

  29. Mancia G, Ferrari A, Gregorini L, et al.: Blood pressure and heart rate variabilities in normotensive and hypertensive human beings. Circ Res 1983, 53:96–104.

    PubMed  CAS  Google Scholar 

  30. Julius S, Jamerson K, Mejia A, et al.: The association of borderline hypertension with target organ changes and higher coronary risk: Tecumseh Blood Pressure Study. JAMA 1990, 264:354–358.

    Article  PubMed  CAS  Google Scholar 

  31. Smith SD, Julius S, Jamerson K, et al.: Hematocrit levels and physiologic factors in relationship to cardiovascular risk in Tecumseh, Michigan. Hypertension 1994, 12:455–462.

    CAS  Google Scholar 

  32. Palatini P, Casiglia E, Pauletto P, et al.: Relationship of tachycardia with high blood pressure and metabolic abnormalities. A study with mixture analysis in three populations. Hypertension 1997, 30:1267–1273.

    PubMed  CAS  Google Scholar 

  33. Deibert DC, DeFronzo RA: Epinephrine-induced insulin resistance in man. J Clin Invest 1980, 65:717–721.

    Article  PubMed  CAS  Google Scholar 

  34. Zeman RJ, Ludemann R, Easton TG, Etlinger JD: Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta-2-receptor agonist. Am J Physiol 1988, 254:E726–E732.

    PubMed  CAS  Google Scholar 

  35. Flaa A, Aksnes TA, Kjeldsen SE, et al.: Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study. Metabolism 2008, 57:1422–1427.

    Article  PubMed  CAS  Google Scholar 

  36. Jamerson KA, Julius S, Gudbrandsson T, et al.: Reflex sympathetic activation induces acute insulin resistance in the human forearm. Hypertension 1993, 21:618–623.

    PubMed  CAS  Google Scholar 

  37. Juhlin-Dannfelt A, Frisk-Holmberg M, Karlsson J, Tesch P: Central and peripheral circulation in relation to muscle-fibre composition in normo- and hyper-tensive man. Clin Sci (Lond) 1979, 56:335–340.

    CAS  Google Scholar 

  38. Tarazi RC, Frohlich ED, Dustan HP: Plasma volume in men with essential hypertension. N Engl J Med 1968, 278:762–765.

    Article  PubMed  CAS  Google Scholar 

  39. Cohn JN: Relationship of plasma volume changes to resistance and capacitance vessel effects of sympathomimetic amines and angiotensin in man. Clin Sci 1966, 30:267–278.

    PubMed  CAS  Google Scholar 

  40. Julius S, Pascual AV, Abbrecht P, London R: Effect of beta-adrenergic blockade on plasma volume in human subjects. Proc Soc Exp Biol Med 1972, 140:982–985.

    PubMed  CAS  Google Scholar 

  41. Julius S, Li Y, Brant D, et al.: Neurogenic pressor episodes fail to cause hypertension, but do induce cardiac hypertrophy. Hypertension 1989, 13:422–429.

    PubMed  CAS  Google Scholar 

  42. Hartford M, Wikstrand J, Wallentin I, et al.: Left ventricular mass in middle-aged men. Relationship to blood pressure, sympathetic nervous activity, hormonal and metabolic factors. Clin Exper Hypertens 1983, 5:1429–1451.

    Article  CAS  Google Scholar 

  43. Lantelme P, Milon H, Gharib C, et al.: White coat effect and reactivity to stress: cardiovascular and autonomic nervous system responses. Hypertension 1998, 31:1021–1029.

    PubMed  CAS  Google Scholar 

  44. Landsberg L: A teleological view of obesity, diabetes and hypertension. Clin Exp Pharmacol Physiol 2006, 33:863–867.

    Article  PubMed  CAS  Google Scholar 

  45. Kannel WB, Brand N, Skinner JJ Jr, et al.: The relation of adiposity to blood pressure and development of hypertension. Ann Intern Med 1967, 67:48–59.

    PubMed  CAS  Google Scholar 

  46. Julius S, Valentini M, Palatini P: Overweight and hypertension: a 2-way street? Hypertension 2000, 35:807–813.

    PubMed  CAS  Google Scholar 

  47. Stein CM, Nelson R, Deegan R, et al.: Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension. J Clin Invest 1995, 96:579–585.

    Article  PubMed  CAS  Google Scholar 

  48. Valentini M, Julius S, Palatini P, et al.: Attenuation of haemodynamic, metabolic and energy expenditure responses to isoproterenol in patients with hypertension. J Hypertens 2004, 22:1999–2006.

    Article  PubMed  CAS  Google Scholar 

  49. Narkiewicz K, Phillips BG, Kato M, et al.: Gender-selective interaction between aging, blood pressure, and sympathetic nerve activity. Hypertension 2005, 45:522–525.

    Article  PubMed  CAS  Google Scholar 

  50. Hogarth AJ, Mackintosh AF, Mary DA: Gender-related differences in the sympathetic vasoconstrictor drive of normal subjects. Clin Sci (Lond) 2007, 112:353–361.

    Google Scholar 

  51. Hogarth AJ, Burns J, Mackintosh AF, Mary DA: Sympathetic nerve hyperactivity of essential hypertension is lower in postmenopausal women than men. J Hum Hypertens 2008, 22:544–549.

    Article  PubMed  CAS  Google Scholar 

  52. Palatini P: Heart rate as a cardiovascular risk factor: Do women differ from men? Ann Med 2001, 33:213–221.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paolo Palatini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palatini, P., Julius, S. The role of cardiac autonomic function in hypertension and cardiovascular disease. Current Science Inc 11, 199–205 (2009). https://doi.org/10.1007/s11906-009-0035-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-009-0035-4

Keywords

Navigation